ESPE Abstracts (2022) 95 P1-303

ESPE2022 Poster Category 1 GH and IGFs (27 abstracts)

Short stature due to a novel missense variant (695C>A) in the GHR gene: a case report.

Beatrice Righi 1 , Gabriele Trimarchi 2 , Alessandro De Fanti 1 , Livia Garavelli 2 , Chiara Sartori 1 & Maria Elisabeth Street 3

1Department of Mother and Child, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy; 2Clinical Genetics Unit, Azienda USL-IRCCS of Reggio Emilia, Reggio Emilia, Italy; 3Unit of Paediatrics, Department of Medicine and Surgery, University of Parma, Parma, Italy

Introduction: Laron Syndrome (LS) or primary growth hormone (GH) insensitivity is an autosomal recessive disorder due to variants in the GH-receptor (GHR) gene or to post-receptor defects. LS prevalence is estimated 1-9/1000000. We report a case of LS with a missense variant in the GHR gene not previously described.

Case: female, Turkish, was referred to our clinic for short stature. Born at term, birth weight was 3890 g (1.68 SDS), length 48 cm (-0.83 SDS) and head circumference 36 cm (1.72 SDS). The parents are first cousins; target height was 160 cm (-0.44 SDS). At first evaluation at 8 months: length 59,7 cm (-4.15 SDS), weight 6.5 kg (-1.86 SDS), head circumference 42 cm (-1.24 SDS), prepubertal. The phenotype was characterized by frontal bossing, midface retrusion, depressed nasal bridge, chubby cheeks, thin lower lip, downturned mouth cornersface. Bone age was 6 months according to Greulich & Pyle atlas. The hematological tests showed low IGF-1 (10 ng/ml, range 8-131) and IGFBP3 (385 ng/ml, range 710-2760) levels, compared to laboratory reference values for sex and age. Due to a relevant reduction of growth velocity in the following six months (4.26 cm/yr, -5.02 SDS) a GH stimulation test was performed with normal GH peak (GH 38.9 ng/ml). Brain MRI was normal. Karyotype was 46,XX. Clinical Exome Sequencing showed the homozygous missense variant c.695 C>A (P.Ser232Tyr) in the GHR gene, yet undescribed. The parents were heterozygous carriers of the same variant. At the age of 2 years and 2 months, the baby started therapy with subcutaneous injections of mecasermin (starting dose 0.04 mg/kg twice daily), showing improvement in growth velocity and muscular tone. Dietary indications with adequate caloric intake, in order to prevent hypoglycaemia, were provided and specific evaluations (cardiological, ophthalmological and ENT evaluations) are regularly performed according to the treatment protocol.

Discussion: LS is characterised by a typical phenotype associated with biochemical findings such as high serum GH and low levels of IGF-1 More than 70 variants, ranging from deletions to point mutations including missense, nonsense, frameshift and splice-site variants, have been previously identified. Therapy with recombinant IGF-1 improves height, metabolic parameters and motor development. Our case presented clinical characteristics of LS (dwarfism, typical phenotype), the diagnosis was confirmed biochemically and genetically, and therapy was started early. It is interesting to underline the importance of surveillance of these patients to optimize therapy and prevent potential adverse consequences.

Volume 95

60th Annual ESPE (ESPE 2022)

Rome, Italy
15 Sep 2022 - 17 Sep 2022

European Society for Paediatric Endocrinology 

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